What causes thrombophilia?

From the Guidelines

Thrombophilia is primarily caused by inherited or acquired conditions that increase the risk of developing venous thrombosis, including factor V Leiden, prothrombin gene mutation, antithrombin deficiency, protein C deficiency, and protein S deficiency, as well as acquired conditions such as antiphospholipid antibodies, cancer, surgery, and oral contraceptives 1.

Inherited Causes

• Factor V Leiden (R506Q) mutation: the most common known inherited risk factor for thrombosis, resulting from a base change from G to A at position 1691 of the gene encoding coagulation Factor V, leading to increased thrombin generation and clot formation 1.
• Prothrombin gene (G20210A) mutation: the second most common known inherited risk factor for thrombosis, resulting in higher circulating prothrombin levels and an enhanced potential for clot formation 1.
• Antithrombin deficiency: a rare inherited condition that increases the risk of thrombosis by 15-20 times 1.
• Protein C deficiency: a rare inherited condition that increases the risk of thrombosis by 15-20 times 1.
• Protein S deficiency: a rare inherited condition that increases the risk of thrombosis by 15-20 times 1.

Acquired Causes

• Antiphospholipid antibodies: acquired conditions that increase the risk of thrombosis by 3-10 times 1.
• Cancer: increases the risk of thrombosis due to tumor-related factors and chemotherapy 1.
• Surgery: increases the risk of thrombosis due to immobilization and tissue damage 1.
• Oral contraceptives: increase the risk of thrombosis by 3-4 times, especially in women with congenital thrombophilia 1.
• Hormone replacement therapy: increases the risk of thrombosis by 3 times, especially in women with a history of thrombosis 1.

From the Research

Causes of Thrombophilia

Thrombophilia can be caused by a combination of inherited and acquired factors. The following are some of the known causes:

• Inherited factors:
  • Deficiencies of natural anticoagulants such as antithrombin, protein C, and protein S 2, 3, 4, 5
  • Increased values of clotting factors, especially factor VIII 2
  • Prothrombotic polymorphisms in genes encoding for factor V (i.e., factor V Leiden) and prothrombin 2, 3, 6
• Acquired factors:
  • Antiphospholipid antibody syndrome 2, 4
  • Malignancy 2
  • Acquired elevations of coagulation factors or acquired reduction of natural inhibitors 2
  • Hyperhomocysteinemia 2, 4

Risk Factors for Thrombophilia

Certain risk factors can increase the likelihood of developing thrombophilia, including:

• Pregnancy, including the puerperium 3
• Surgery 3, 4
• Oral contraceptive usage 3, 6
• Prolonged periods of immobilization 3
• Smoking 6
• Family history of thrombophilia 3, 4, 5

Classification of Thrombophilia

Thrombophilia can be classified into two main categories:

• Inherited (or genetically determined) thrombophilia 2, 3, 4, 5
• Acquired thrombophilia 2, 4